About Paroxysmal Nocturnal Hemoglobinuria
What is PNH?
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening blood disorder characterized by the complement-mediated destruction (hemolysis) of oxygen-carrying red blood cells. The disease is caused by a genetic mutation in the DNA and causes red blood cells to be missing a critical protein responsible for protecting them.
Hemolysis occurs in PNH through two mechanisms: intravascular hemolysis (IVH), which occurs inside blood vessels, and extravascular hemolysis (EVH), which occurs in the liver and spleen. Both types of hemolysis are responsible for the symptoms of PNH. When red blood cells break apart, hemoglobin (carries oxygen around the body) is eliminated in urine. Low hemoglobin leads to low oxygen, which causes symptoms like fatigue, headache, and shortness of breath.1
Prevalence & Diagnosis
PNH is believed to affect males and females equally, although some studies have shown a slight preponderance in females. The prevalence is estimated to be between 0.5-1.5 per million people in the general population. The disorder has been described in many racial groups and has been identified in all areas of the world. The median age at diagnosis is during the 30s.2
PNH diagnosis may be suspected in individuals who have symptoms of intravascular hemolysis (e.g., hemoglobinuria, abnormally high serum LDH concentration) with no known cause. The diagnosis may be made based upon a thorough clinical evaluation, detailed patient history, and/or a variety of specialized tests. The main diagnostic test for individuals with suspected PNH is flow cytometry, a blood test that can identify PNH cells (blood cells that are missing GPI-anchored proteins).2
Symptoms
PNH has a wide range of symptoms, so it is not unusual for months or years to pass before the correct diagnosis is established.
Overall, the most common symptoms of PNH include:3
Significant fatigue or weakness
Bruising or bleeding easily
Shortness of breath
Recurring infections and/or flu-like symptoms
Difficulty in controlling bleeding, even from very minor wounds
The appearance of small red dots on the skin that indicates bleeding under the skin
Severe headache
Fever due to infection
Blood clots (thrombosis)
PNH Treatment Options
The appropriate treatment for PNH depends on the severity of symptoms. Some patients will experience few or no symptoms and do not require treatment other than potential vitamin supplements.
Medical Therapy
The main treatment for PNH is medicine to stop the breakdown of red blood cells, lower chances of blood clots, and improve the quality of life. There are currently three drugs approved to treat PNH. They work by binding to complement proteins in the body. This binding reduces complement-mediated hemolysis, which is the cause of the health problems in PNH.3,4
Empaveli®/Aspaveli® (Pegcetacoplan), one the three drugs, is cleared for use with the FreedomEdge Infusion system in EU and pending 510k clearance in US. The FreedomEdge® Syringe Infusion System was used during PEGASUS clinical trial for Empaveli/Aspaveli along with F2400 Precision Flow Rate Tubing™ and 1 or 2-leg, 26G HIgH-Flo Subcutaneous Safety Needle Sets™.
Allogeneic Bone Marrow Transplantation
Allogeneic bone marrow transplantation is the only cure for PNH as it replaces all the patient’s bone marrow stem cells with those from a donor. This may be appropriate for those not responding to eculizumab or for those who have severe reductions in red blood cells, white blood cells and platelets and is best reserved for young patients with a very severe diagnosis.3
References
- Apellis. For Patients. Paroxysmal Nocturnal Hemoglobinuria (PNH). https://apellis.com/for-patients/understanding-paroxysmal-nocturnal-hemoglobinuria-pnh/ Accessed 18 Mar 2022
- Paroxysmal Nocturnal Hemoglobinuria. https://rarediseases.org/rare-diseases/paroxysmal-nocturnal-hemoglobinuria. Accessed 14 Feb 2022
- Paroxysmal Nocturnal Hemoglobinuria (PNH). https://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/paroxysmal_nocturnal_hemoglobinuria_PNH.html Accessed 11 Mar 2021
- How Empaveli works. https://empaveli.com/how-it-works/ Accessed 18 Mar 2022.
Related Publications & Educational Materials
Hillmen et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. NEJM; 2021:1028-1037. https://www.nejm.org/doi/full/10.1056/NEJMoa2029073
Sharma VR. Paroxysmal nocturnal hemoglobinuria: Pathogenesis, testing, and diagnosis. Clin Adv Hematol Oncol. 2013;11:1-11 https://www.hematologyandoncology.net/files/2013/10/ho0913_PNH_sup133.pdf
Resources
FreedomEdge Step-by-Step SubQ Guide
Use this tool to help walk you through your subQ infusions with the FreedomEdge® for the administration of pegcetacoplan (Aspaveli®/Empaveli®).
Download
This is PNH
Join the PNH community to learn, connect and share: an opportunity to explore new information, gather ideas and support one another along the way.
https://thisispnh.com/
Rare Disease Database
Learn more about Paroxysmal Nocturnal Hemoglobinuria.
rarediseases.org
About Soliris® (eculizumab)
Learn more about this medical treatment indicated for PNH.
alexion.com
About Ultomiris® (ravulizumab‑cwvz)
Learn more about this medical treatment indicated for PNH.
ultomiris.com
About Empaveli® (pegcetacoplan)
EMPAVELI was studied vs eculizumab in a head-to-head Phase 3 clinical trial in 80 people living with PNH. Learn more about this subcutaneous therapy option for the treatment of PNH.
empaveli.com